title: OS9 interacts with DC-STAMP and modulates its intracellular localization in response to TLR ligation.
abstract: Dendritic cell-specific transmembrane protein (DC-STAMP) has been first identified as an EST in a cDNA library of human monocyte-derived dendritic cells (DC). DC-STAMP is a multimembrane spanning protein that has been implicated in skewing haematopoietic differentiation of bone marrow cells towards the myeloid lineage, and in cell fusion during osteoclastogenesis and giant cell formation. To gain molecular insight in how DC-STAMP exerts its function, DC-STAMP interacting proteins were identified in a yeast-2-hybrid analysis. Herein, we report that amplified in osteosarcoma 9 (OS9) physically interacts with DC-STAMP, and that both proteins colocalize in the endoplasmic reticulum in various cell lines, including immature DC. OS9 has previously been implicated in ER-to-Golgi transport and transcription factor turnover. Interestingly, we now demonstrate that toll-like receptor (TLR)-induced maturation of DC leads to the translocation of DC-STAMP from the ER to the Golgi while OS9 localization is unaffected. Applying TLR-expressing CHO cells we could confirm ER-to-Golgi translocation of DC-STAMP following TLR stimulation and demonstrated that the DC-STAMP/OS9 interaction is involved in this process. Collectively, the data indicate that OS9 is critically involved in the modulation of ER-to-Golgi transport of DC-STAMP in response to TLR triggering, suggesting a novel role for OS9 in myeloid differentiation and cell fusion.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Bastiaan J H
authors.initials: BJ
authors.lastname: Jansen
authors.forename: Dagmar
authors.initials: D
authors.lastname: Eleveld-Trancikova
authors.forename: Anna
authors.initials: A
authors.lastname: Sanecka
authors.forename: Maaike
authors.initials: M
authors.lastname: van Hout-Kuijer
authors.forename: Ilona A M
authors.initials: IA
authors.lastname: Hendriks
authors.forename: Maaike G W
authors.initials: MG
authors.lastname: Looman
authors.forename: Jeanette H W
authors.initials: JH
authors.lastname: Leusen
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D037102:Lectins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501589:DCSTAMP protein, human; D037102:Lectins; D008565:Membrane Proteins; D050505:Mutant Proteins; D009363:Neoplasm Proteins; C098898:OS9 protein, human; D011993:Recombinant Fusion Proteins; D051193:Toll-Like Receptors